Human skin undergoes changes with age due to various intrinsic and extrinsic factors. With respect to the intrinsic factors, the secretion of various hormones regulating metabolism is reduced, and the function of immune cells and the activity of cells are reduced, thus reducing the biosynthesis of immune proteins required in vivo and bioproteins. With respect to the extrinsic factors, environmental pollution and UV light cause various changes, including an increase in wrinkles, a reduction in elasticity, dry skin, and increases in melasma, freckles and age spots, leading to skin deterioration. These days, because most people want to look young and beautiful, they have a strong need to prevent or ameliorate skin aging due to extrinsic factors, such as UV and stress, as well as intrinsic factors.
One of the skin diseases, atopic dermatitis (AD) is a skin disorder with multifactorial etiology, such as immunological, genetic, pharmacological, physiological, and environmental factors, is caused in particular, by infections, stress, changes in season and climate, stimuli, and allergens. Atopic dermatitis is a chronic inflammation of the skin that occurs in persons of all ages, from infants to adults.
In general, approximately 80% of atopic dermatitis is associated with IgE, and atopic dermatitis can be categorized into the extrinsic (IgE-mediated) and the intrinsic (non-IgE-mediated) types. The elevated IgE response and eosinophilia are observed in patients with atopic dermatitis, which reflects increased responses of Th2 cytokines such as IL-4 and IL-5 with a concomitant decrease in the Th1 cytokine, IFN-γ production. In this connection, the use of various immunomodulators such as pime-crolimus and tacrolimus has been attempted. Especially, the presence of CD4+ CD25+ regulatory T cells (Treg cells) capable of directly suppressing immune responses has recently become known. Treg cells originate from the thymus and have an ability to control the activity of various T lymphocytes. Further, Treg cells transduce immune inhibitory signals or inhibit interaction between immune cells such as macrophages or B cells by the expression of CTLA4, GITR, CD25 and LAGS on their surface. Treg cells induce immune suppression through the production of cytokines such as TGF-β and IL-35, in addition to IL-10. In atopic dermatitis, Th2 cytokines such as IL-4 and IL-5 are highly produced due to defects in Th2 cell development, whereas the production of Th1 cytokines such as IFN-γ is suppressed. Recently, it was known that Th2 chemokines, represented by TARC/CCL17, MDC/CCL22, and CTACK/CCL2, directly affect Th2 cell development.
Cytokines are produced by various cells, and have many different actions. In particular, since an identical cytokine may exert different functions, cytokines are very difficult to classify. When T cells recognize antigens presented by macrophages and are activated to induce immune responses, numerous cytokines are involved in this process. Various cytokines are involved in each step of innate and adaptive immunity, from antigen recognition to effector steps, and some cytokines are also involved in the production of lymphocytes and other hemocytes. The actions of key cytokines are as follows.
IL-1 (interleukin 1) is a cytokine that is produced by activated mononuclear phagocytes, epithelial cells, or endothelial cells, and mediates inflammation. There are two forms of IL-1, IL-1α and IL-1β. A small amount of IL-1 activates CD4-T cells and B cells and stimulates inflammatory cells. However, an excessive amount of IL-1 functions as a hormone to induce fever and acute phase response.
IL-4 (interleukin 4) is a protein having a size of approximately 20 kDa, which is produced by CD4 T cells and activated mast cells, and functions as a B-cell growth factor. IL-4 also functions as a differentiation factor involved in immunoglobulin class switching in B cells, and may also activate CD4 T cells, mast cells, macrophages, etc.
IL-10 (interleukin 10) induces differentiation of activated T cells into CTLs by a synergistic effect with IL-2, and also induces proliferation of NK cells, LAK cells, and activated T cells.
IFN-γ (interferon-γ, also known as type II interferon, is produced by CD4 T cells or CD8 T cells to regulate immune responses, and is thus also called immune interferon. IFN-γ acts on T cells, B cells, NK cells, and endothelial cells to activate them, and functions as a macrophage-activating factor to increase the expression of MHC Class I and II. IFN-γ is also able to inhibit viral replication, like other interferons.
NO functions as a vasodilator under physiological conditions. However, when macrophages are stimulated by inflammatory cytokines, NO produced by iNOS induces inflammation under pathological conditions to increase COX-2 (cyclooxygenase-2) activity, leading to amplification of inflammation via arachidonic acid cascade.
COX-2 is a key modulator that produces prostaglandins from arachidonic acid. COX-2 converts arachidonic acid to PGG2. Depending on the enzymes, PGG2 is converted to PGE2, PGD2, PGF2, PGI2, or TXA2, which exert different functions in vivo. A representative COX-2 inhibitor is aspirin.
A recent research trend has focused on up- and down-regulation of IgE production by immune modulation, and the effects of clinically available, oriental herbal medicines on patients with atopic dermatitis have been actively studied. However, there is no report on the efficacy of Chrysanthemum boreale Makino on atopic dermatitis.